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Inhibition of membrane fusion proteins

a technology of membrane fusion and protein, which is applied in the field of viral infection control, can solve the problems of insufficient antiviral strategies and sorely needed alternative strategies, and achieve the effects of inhibiting infection, and reducing quenching of fluorescent molecules

Inactive Publication Date: 2011-08-23
ALBERT EINSTEIN COLLEGE OF MEDICINE OF YESHIVA UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Benefits of technology

The present invention is based on the discovery that a soluble protein from a virus can prevent the virus from infecting a eukaryotic cell. The invention provides methods for using this soluble protein to inhibit viral infection and screen test compounds for their ability to prevent infection. The soluble protein contains a specific domain from the virus's fusion protein, which binds to the virus's core homotrimer, preventing it from infecting the cell. The invention also provides aqueous-soluble proteins that contain a portion of the virus's fusion protein, which can be used to screen test compounds for their ability to prevent infection. The technical effect of the invention is to provide a way to prevent viral infection and screen for potential antiviral compounds.

Problems solved by technology

Dengue is a major global health problem and the estimates are that more than one-third of the world's population lives in dengue fever endemic areas.
While significant research on preventative vaccines is underway, it is complicated by the fact that antibodies can enhance infection leading to DHF and dengue shock syndrome (Rothman and Ennis, 1999).
Control of the mosquito vector is the current mode of prevention but is itself problematic and almost nonexistent in many endemic countries (Weaver and Barrett, 2004).
Thus, alternative antiviral strategies are sorely needed.

Method used

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Domain III from Class III Fusion Proteins Functions as a Dominant-Negative Inhibitor of Virus Membrane Fusion

[0186]Rationale and domain III expression. The structure of the class II homotrimer suggests several features that might be targets for inhibition of the fusion reaction. The pH 7 form of the dengue virus E protein crystallized with a molecule of detergent bound in a hydrophobic pocket near the “hinge” region between domains 1 and II (Modis et al., 2003). As the hinge changes its angle during the transition to the trimer form, inhibition of this flexibility may block fusion and infection. Thus, molecules that dock into the hydrophobic pocket are potential antivirals (Modis et al., 2003). The structure of the fusion protein homotrimer reveals that the “stem” region of the protein interacts (or would be predicted to interact in the case of the dengue HT and TBE HT, which do not contain the stem) with an HT core region composed of domains I and II (see stem in FIG. 3 schematic)....

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Abstract

Methods of inhibiting viral infection of a eukaryotic cell by a target virus having a class II virus fusion protein are provided. Also provided are methods of screening a test compound for the ability to inhibit infection by a virus having a class II viral fusion protein. Additionally provided herewith are aqueous-soluble proteins comprising a portion of a class II viral fusion protein comprising a Domain III of the viral fusion protein.

Description

CROSS-REFERENCE TO RELATED APPLICATION[0001]This is a U.S. national phase of PCT Application No. PCT / US2006 / 017284, filed May 4, 2006, which claims the benefit of U.S. Provisional Application No. 60 / 678,467, filed May 6, 2005.STATEMENT REGARDING FEDERALLY SPONSORED RESEARCH OR DEVELOPMENT[0002]This invention was made with government support under grant number GM52929 awarded by the National Institutes of Health. The government has certain rights in the invention.BACKGROUND OF THE INVENTION[0003](1) Field of the Invention[0004]The present invention generally relates to control of viral infection. More specifically, the invention is directed to control of virus-membrane fusion reactions of viruses having class II fusion proteins, and methods for identifying compounds that effect that control.[0005](2) Description of the Related ArtREFERENCES CITED[0006]Ahn, A., Klimjack, M. R., Chatterjee, P. K., and Kielian, M. (1999). An epitope of the Semliki Forest virus fusion protein exposed dur...

Claims

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Application Information

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Patent Type & Authority Patents(United States)
IPC IPC(8): G01N33/53A61K39/12
CPCA61K38/162G01N2333/005G01N2500/04
Inventor KIELIAN, MARGARETLIAO, MAOFU
Owner ALBERT EINSTEIN COLLEGE OF MEDICINE OF YESHIVA UNIV
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